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Osteopontin Signals through Calcium and Nuclear Factor of Activated T Cells (NFAT) in Osteoclasts
- Source :
- Journal of Biological Chemistry. 286:39871-39881
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Osteopontin (OPN), an integrin-binding extracellular matrix glycoprotein, enhances osteoclast activity; however, its mechanisms of action are elusive. The Ca2+-dependent transcription factor NFATc1 is essential for osteoclast differentiation. We assessed the effects of OPN on NFATc1, which translocates to nuclei upon activation. Osteoclasts from neonatal rabbits and rats were plated on coverslips, uncoated or coated with OPN or bovine albumin. OPN enhanced the proportion of osteoclasts exhibiting nuclear NFATc1. An RGD-containing, integrin-blocking peptide prevented the translocation of NFATc1 induced by OPN. Moreover, mutant OPN lacking RGD failed to induce translocation of NFATc1. Thus, activation of NFATc1 is dependent on integrin binding through RGD. Using fluorescence imaging, OPN was found to increase the proportion of osteoclasts exhibiting transient elevations in cytosolic Ca2+ (oscillations). OPN also enhanced osteoclast survival. The intracellular Ca2+ chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) suppressed Ca2+ oscillations and inhibited increases in NFATc1 translocation and survival induced by OPN. Furthermore, a specific, cell-permeable peptide inhibitor of NFAT activation blocked the effects of OPN on NFATc1 translocation and osteoclast survival. This is the first demonstration that OPN activates NFATc1 and enhances osteoclast survival through a Ca2+-NFAT-dependent pathway. Increased NFATc1 activity and enhanced osteoclast survival may account for the stimulatory effects of OPN on osteoclast function in vivo.
- Subjects :
- musculoskeletal diseases
integumentary system
biology
NFAT
Cell Biology
NFATC Transcription Factors
Biochemistry
Cell biology
chemistry.chemical_compound
medicine.anatomical_structure
stomatognathic system
BAPTA
chemistry
Osteoclast
Cancer research
biology.protein
medicine
Osteopontin
Molecular Biology
Transcription factor
Intracellular
Integrin binding
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 286
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi...........c2e88fe8ad6d69e39fdb42a7b2fb720c